Cocaine Use Disorder
Conditions
Keywords
Transcranial Magnetic Stimulation (TMS)
Brief summary
The purpose of this study is to assess the effects of active intermittent theta burst stimulation (iTBS) to dorsomedial prefrontal cortex (dmPFC) on electroencephalogram (EEG) measures of reward sensitivity and cue reactivity and cocaine craving in cocaine users
Interventions
DEVICEiTBS to dmPFC
TMS will be delivered with a MagVenture Mag Pro R30 with the Cool-B70 A/P coil with active liquid cooling and active/sham sides. Approximately 25% of the nasion-inion distance, or Talairah coordinates X 0 Y+60 Z+60 will be measured.The first session will begin with the acquisition of the resting motor threshold (rMT; lowest stimulus intensity that elicits a visible twitch on 50% of the trials) on the contralateral hand. iTBS (triplet 50 Hz bursts, repeated at 5 Hz, 2 sec on and 8 sec off; 600 pulses per session) will be delivered at 110% of the rMT and will last about 3 minutes. Each participant will receive 2 sessions with a 15-20 minute interval between sessions.
DEVICESham iTBS
Sham TMS will be delivered with the sham side of the MagVenture Cool B70 A/P coil. The software will be pre-programmed by a staff member that will not be involved in data analysis or collection for blinding purposes. The sham stimulation will match the number of pulses and length of time as the active condition and each participant will receive 2 sessions with a 15-20 min interval between sessions.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* CUD diagnosis
Exclusion criteria
* moderate or severe criteria for substances other than cocaine, cannabis, or nicotine * unstable psychiatric disorder * medical conditions contraindicated to TMS (e.g., medical implants, history of seizure or seizure disorder, medications lowering the seizure threshold, neurological conditions, moderate-to-severe heart disease) * pregnancy * hairstyles incompatible with the EEG net * head injury with loss of consciousness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | Baseline (before iTBS session) | The Doors Task will be used to elicit the Reward Potential (RewP) component, representing reward sensitivity. The task is a guessing game, where participants guess which door contains a reward behind it. After selecting a door, the participants are notified if they found the prize by a green arrow pointing up or if they did not find the prize by a red arrow pointing down. The amplitude of the RewP in microvolts in response to feedback is reported. |
| Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | Baseline (before iTBS session) | The Picture Viewing Task will be used to elicit the late positive potential (LPP), reflecting the motivational salience of a stimulus. During this task, participants are asked to view a slideshow of images including pleasant, unpleasant, neutral, and cocaine-related images. The amplitude of the LPP in microvolts in response to visual stimuli is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS) | Baseline(before iTBS session) | The first question (intensity of craving) will be used and is measured from 0(none, not at all) to 100(a great deal), higher number indicating more craving. |
| Pain as Assessed by the Visual Analog Scale (VAS) | Baseline(before iTBS session) | This is scored from 0(no pain) to 10 (worst pain), higher score indicating greater pain. |
| Cognitive Function as Assessed by the Montreal Cognitive Assessment (MoCA) | Baseline(before iTBS session) | Total score on the Montreal Cognitive Assessment (MoCA) range from 0 to 30, with a higher score indicating a better outcome. |
| Cognitive Function as Assessed by the The Montreal Cognitive Assessment (MoCA) | Immediately after iTBS session | Total score on the Montreal Cognitive Assessment (MoCA) range from 0 to 30, with a higher score indicating a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| iTBS to dmPFC, Then Sham iTBS iTBS to dmPFC: TMS will be delivered with a MagVenture Mag Pro R30 with the Cool-B70 A/P coil with active liquid cooling and active/sham sides. Approximately 25% of the nasion-inion distance, or Talairah coordinates X 0 Y+60 Z+60 will be measured.The first session will begin with the acquisition of the resting motor threshold (rMT; lowest stimulus intensity that elicits a visible twitch on 50% of the trials) on the contralateral hand. iTBS (triplet 50 Hz bursts, repeated at 5 Hz, 2 sec on and 8 sec off; 600 pulses per session) will be delivered at 110% of the rMT and will last about 3 minutes. Each participant will receive 2 sessions with a 15-20 minute interval between sessions.
Sham iTBS: Sham TMS will be delivered with the sham side of the MagVenture Cool B70 A/P coil. The software will be pre-programmed by a staff member that will not be involved in data analysis or collection for blinding purposes. The sham stimulation will match the number of pulses and length of time as the active condition and each participant will receive 2 sessions with a 15-20 min interval between sessions. | 3 |
| Sham iTBS, Then iTBS to dmPFC iTBS to dmPFC: TMS will be delivered with a MagVenture Mag Pro R30 with the Cool-B70 A/P coil with active liquid cooling and active/sham sides. Approximately 25% of the nasion-inion distance, or Talairah coordinates X 0 Y+60 Z+60 will be measured.The first session will begin with the acquisition of the resting motor threshold (rMT; lowest stimulus intensity that elicits a visible twitch on 50% of the trials) on the contralateral hand. iTBS (triplet 50 Hz bursts, repeated at 5 Hz, 2 sec on and 8 sec off; 600 pulses per session) will be delivered at 110% of the rMT and will last about 3 minutes. Each participant will receive 2 sessions with a 15-20 minute interval between sessions.
Sham iTBS: Sham TMS will be delivered with the sham side of the MagVenture Cool B70 A/P coil. The software will be pre-programmed by a staff member that will not be involved in data analysis or collection for blinding purposes. The sham stimulation will match the number of pulses and length of time as the active condition and each participant will receive 2 sessions with a 15-20 min interval between sessions. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (2 Sessions) | excluded after randomization due to high blood pressure | 0 | 1 |
Baseline characteristics
| Characteristic | iTBS to dmPFC, Then Sham iTBS | Total | Sham iTBS, Then iTBS to dmPFC |
|---|---|---|---|
| Age, Continuous | 51.7 years STANDARD_DEVIATION 9.9 | 45.8 years STANDARD_DEVIATION 11.16 | 37.0 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
| Years of Education | 12 years STANDARD_DEVIATION 0 | 11.4 years STANDARD_DEVIATION 1.2 | 10.5 years STANDARD_DEVIATION 1.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG
The Picture Viewing Task will be used to elicit the late positive potential (LPP), reflecting the motivational salience of a stimulus. During this task, participants are asked to view a slideshow of images including pleasant, unpleasant, neutral, and cocaine-related images. The amplitude of the LPP in microvolts in response to visual stimuli is reported.
Time frame: Baseline (before iTBS session)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Pleasant Images | 1.10 microvolts | Standard Deviation 1.4 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Unpleasant Images | 1.01 microvolts | Standard Deviation 2.04 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Cocaine Images | .61 microvolts | Standard Deviation 1.49 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Neutral Images | -0.35 microvolts | Standard Deviation 1.51 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Neutral Images | -0.95 microvolts | Standard Deviation 2.23 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Pleasant Images | 0.37 microvolts | Standard Deviation 1.85 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Cocaine Images | 0.46 microvolts | Standard Deviation 1.81 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Unpleasant Images | 0.40 microvolts | Standard Deviation 2.55 |
Primary
Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG
The Picture Viewing Task will be used to elicit the late positive potential (LPP), reflecting the motivational salience of a stimulus. During this task, participants are asked to view a slideshow of images including pleasant, unpleasant, neutral, and cocaine-related images. The amplitude of the LPP in microvolts in response to visual stimuli is reported.
Time frame: Immediately after iTBS session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Pleasant Images | .66 microvolts | Standard Deviation 1.48 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Unpleasant Images | 1.11 microvolts | Standard Deviation 1.73 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Cocaine Images | 1.02 microvolts | Standard Deviation 1.31 |
| iTBS to dmPFC | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Neutral Images | -0.28 microvolts | Standard Deviation 1.21 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Neutral Images | -0.0000929 microvolts | Standard Deviation 1.39 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Pleasant Images | .19 microvolts | Standard Deviation 1.78 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Cocaine Images | .43 microvolts | Standard Deviation 0.43 |
| Sham iTBS | Amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG | LPP Amplitude with Unpleasant Images | .78 microvolts | Standard Deviation 1.67 |
Primary
Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG
The Doors Task will be used to elicit the Reward Potential (RewP) component, representing reward sensitivity. The task is a guessing game, where participants guess which door contains a reward behind it. After selecting a door, the participants are notified if they found the prize by a green arrow pointing up (win) or if they did not find the prize by a red arrow pointing down (loss). The amplitude of the RewP in microvolts in response to feedback is reported.
Time frame: Immediately after iTBS session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| iTBS to dmPFC | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Win | -1.10 microvolts | Standard Deviation 1.54 |
| iTBS to dmPFC | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Loss | -1.30 microvolts | Standard Deviation 1.05 |
| Sham iTBS | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Win | 0.21 microvolts | Standard Deviation 1.76 |
| Sham iTBS | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Loss | 0.02 microvolts | Standard Deviation 1.37 |
Primary
Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG
The Doors Task will be used to elicit the Reward Potential (RewP) component, representing reward sensitivity. The task is a guessing game, where participants guess which door contains a reward behind it. After selecting a door, the participants are notified if they found the prize by a green arrow pointing up or if they did not find the prize by a red arrow pointing down. The amplitude of the RewP in microvolts in response to feedback is reported.
Time frame: Baseline (before iTBS session)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| iTBS to dmPFC | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Win | -1.09 microvolts | Standard Deviation 1.95 |
| iTBS to dmPFC | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Loss | -0.23 microvolts | Standard Deviation 2.15 |
| Sham iTBS | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Win | 0.61 microvolts | Standard Deviation 1.8 |
| Sham iTBS | Amplitude of the Reward Potential (RewP) in Microvolts in Response to Feedback on the Doors Task as Assessed by EEG | RewP Amplitude with Loss | 0.12 microvolts | Standard Deviation 1.75 |
Secondary
Cognitive Function as Assessed by the Montreal Cognitive Assessment (MoCA)
Total score on the Montreal Cognitive Assessment (MoCA) range from 0 to 30, with a higher score indicating a better outcome.
Time frame: Baseline(before iTBS session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Cognitive Function as Assessed by the Montreal Cognitive Assessment (MoCA) | 23 score on a scale | Standard Deviation 4.05 |
| Sham iTBS | Cognitive Function as Assessed by the Montreal Cognitive Assessment (MoCA) | 22.8 score on a scale | Standard Deviation 4.96 |
Secondary
Cognitive Function as Assessed by the The Montreal Cognitive Assessment (MoCA)
Total score on the Montreal Cognitive Assessment (MoCA) range from 0 to 30, with a higher score indicating a better outcome.
Time frame: Immediately after iTBS session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Cognitive Function as Assessed by the The Montreal Cognitive Assessment (MoCA) | 22.4 score on a scale | Standard Deviation 3.01 |
| Sham iTBS | Cognitive Function as Assessed by the The Montreal Cognitive Assessment (MoCA) | 25 score on a scale | Standard Deviation 2.76 |
Secondary
Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS)
The first question (intensity of craving) will be used and is measured from 0(none, not at all) to 100(a great deal), higher number indicating more craving.
Time frame: Immediately after iTBS session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS) | 33.8 score on a scale | Standard Deviation 37.81 |
| Sham iTBS | Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS) | 18 score on a scale | Standard Deviation 26.39 |
Secondary
Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS)
The first question (intensity of craving) will be used and is measured from 0(none, not at all) to 100(a great deal), higher number indicating more craving.
Time frame: Baseline(before iTBS session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS) | 41 score on a scale | Standard Deviation 39.08 |
| Sham iTBS | Craving as Assessed by the Minnesota Cocaine Craving Scale (MCCS) | 31.2 score on a scale | Standard Deviation 38.55 |
Secondary
Pain as Assessed by the Visual Analog Scale (VAS)
This is scored from 0(no pain) to 10 (worst pain), higher score indicating greater pain.
Time frame: Baseline(before iTBS session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Pain as Assessed by the Visual Analog Scale (VAS) | 0.6 score on a scale | Standard Deviation 1.2 |
| Sham iTBS | Pain as Assessed by the Visual Analog Scale (VAS) | 0.2 score on a scale | Standard Deviation 0.4 |
Secondary
Pain as Assessed by the Visual Analog Scale (VAS)
This is scored from 0(no pain) to 10 (worst pain), higher score indicating greater pain.
Time frame: Immediately after iTBS session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| iTBS to dmPFC | Pain as Assessed by the Visual Analog Scale (VAS) | 2 score on a scale | Standard Deviation 3.52 |
| Sham iTBS | Pain as Assessed by the Visual Analog Scale (VAS) | 1.6 score on a scale | Standard Deviation 1.74 |